Broad, long-term objective: To determine the neural mechanisms that subserve learning, extinction and spontaneous recovery (SR) of a conditioned taste aversion (CTA). Evidence suggests that the expression of c-Fos [i.e., the protein produced by the immediate-early gene (lEG) c-fos] may mediate sensory experience as well as the formation of CTAs. The proposed work combines behavioral and immunohistochemical methods in order to explore the role of this lEG in learning, extinction and SR. Background: While a great deal of effort has gone into discovering the means by which the brain remembers new information, relatively little work has addressed the processes by which the brain discards or discounts less useful data. It is uncertain whether the process of extinction represents an "unlearning" of material or if it is an acquisition of new information suggesting that the old material, while retained, is no longer useful. There is empirical evidence on both sides of this issue. The study of the brain mechanisms that mediate spontaneous recovery (SR) of an extinguished response will inform this controversy. Methods and Objectives: We will create CTAs in rats by pairing the taste of saccharin (SAC; CS) with an i.p. injection of Lithium Chloride (LiCI; US) and then administer extinction trials (i.e., give access to the SAC solution without the LiCI). SR of the CTA will be measured following a period of days when the extinguished rats will be allowed to drink water before a final day in which SAC is offered. Additional conditioned, yoked controls and explicitly unpaired CS-US yoked controls will/will not receive extinction trials or SR treatments. Following the SR test, brains of experimental subjects and yoked controls will be prepared for c-Fos assays. The objectives of the proposed work include: (1) Identifying brain areas important in the acquisition, extinction, and SR of a CTA as well as in the sensation of the CS and US; (2) Documenting the relationship between CTA acquisition/extinction/SR and c- Fos protein expression in a variety of brain areas known to be involved in this form of learning. Health relatedness: This project will reveal how the brain either "unlearns" or differentially encodes new meanings associated with a previously learned response. The work will advance the development of treatments for various neurological disorders, deficits in extinction (e.g., posttraumatic stress disorder) and conditioned aversions associated with cancers.